Discovery of 2-(1,2,4-triazol-3-yl)pyridine KTD-092 as a novel DYRK1A inhibitor

Abstract

Dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A) is a protein kinase that is ubiquitously expressed in human tissues and acts as a master regulator of cell proliferation and differentiation. DYRK1A might be associated with Down syndrome (DS), Alzheimer's disease (AD), autism spectrum disorder (ASD), diabetes and other neurodegenerative diseases. In search of novel and selective DYRK1A inhibitor scaffold, KTD-092 are validated as a hit for DYRK1A inhibition. KTD-092 shows good stability under various liver microsomes, and markedly reduces tau phosphorylation in a human neuroblastoma cell in a concentration-dependent manner. Molecular binding mode of KTD-092 to DYRK1A is also proposed.